基于两样本孟德尔随机化法探索儿童期肥胖和子痫前期的因果关系

Exploring the causal relationship between childhood obesity and pre-eclampsia based on two-sample Mendelian randomization approach

目的观察性研究表明儿童期肥胖与子痫前期的发生有一定关系,然而其因果关系仍不清楚。本研究采用两样本孟德尔随机化设计,利用公开的全基因组关联研究(GWAS)数据评估儿童期肥胖与子痫前期之间的因果关系。方法儿童期体重指数(n=61111)的GWAS汇总数据来自GWAS-meta分析。子痫前期(6663例病例和194266例对照)的汇总数据来自FinnGen基因组研究项目网站。采用逆方差加权(IVW)作为主要分析,并进行敏感性分析以评估研究结果的稳健性。结果IVW支持儿童期肥胖与子痫前期风险之间的因果关系(OR=1.40,95%CI=1.14~1.72,P=0.001)。敏感性分析进一步支持研究结果的稳健性。结论儿童期肥胖与子痫前期风险增加有关,因此建议肥胖儿童早期采取有效的体重干预措施以降低未来发生不良妊娠结局的风险。

Objective Observational studies have shown an association between childhood obesity and the occurrence of pre-eclampsia(PE),but the causal relationship remains unclear.In this study,a two-sample Mendelian randomization design was used to assess the causal relationship between childhood obesity and PE using data from the publicly available Genome-Wide Association Study(GWAS).Methods GWAS summary statistics of childhood body mass index(n=61111)were derived from the GWAS-meta analysis.The pooled statistics for PE(6663 cases and 194266 controls)were obtained from the FinnGen Genome Project website.Inverse variance weighting(IVW)was used as the main analysis,and sensitivity analyses was performed to assess the robustness of the findings.Results IVW supported the causal association between childhood obesity and the risk of PE(OR=1.40,95%CI=1.14~1.72,P=0.001).The sensitivity analyses furthers support the robustness of the research findings.Conclusion Childhood obesity is associated with an increased risk of PE.It is recommended that obese children take effective weight interventions early to reduce the risk of adverse pregnancy outcomes in the future.